The goal of the research projects outlined in this proposal is the design, discovery, development, and application of practical catalysts that selectively generate chiral molecules in optically active form. Increasing awareness of the importance of absolute stereochemistry in drug function provides the major driving force behind efforts in asymmetric catalysts. In addition, fundamental mechanistic insights may be derived from highly stereoselective processes. A highly mechanistic approach to catalyst design is adopted in this research program, with application of through use of binding studies, kinetics, structural work, the study of model systems, and other tools of physical organic chemistry to elucidate and control the factors that determine selectivity. The broad, long-term objectives of this research include: a) the evaluation of fundamentally new strategies for catalyst design, b) the discovery and development of catalysts for asymmetric organic reaction of broad synthetic importance, c) the elucidation of the mechanism of reaction of the catalysts that are discovered in this research, and d) illustration of the utility of these catalysts through their application in the synthesis of biologically important targets. The specific aims of this project involve various approaches to catalyst design. Recently developed asymmetric epoxidation catalysts serve as a basis for directed toward attainment of high enantioselectivity in the oxidation of alkyl-substituted alkenes and mono-substituted olefins. Evaluation and development of biological oxidation catalysts such as chloroperoxidase is also undertaken. New catalytic strategies are also presented for accomplishing selective transformation of enantiomerically enriched epoxides now accessible via(salen)Mn-and chloroperoxidase- catalyzed epoxidation. Recently-discovered catalysts for enantioselective aziridination employ remarkably simple and synthetically accessible bisimine ligands. Mechanistic and synthetic strategies based on these ligands for developing aziridination catalysts of practical utility are presented. Bisimine ligands will also be evaluated as ligands in other synthetically important asymmetric reactions, such as chiral Lewis acid catalyzed processes. In a final section of the proposal, a new strategy for designing and developing asymmetric catalysts is advanced, based on the Pauling model for enzymatic catalysis.